Hepatitis B viral infection remains an important cause of chronic liver disease and liver cancer, affecting approximately 2 million Americans and more than 350 million people worldwide. Despite vaccine discovery, the burden of chronic, often lifelong hepatitis B infection remains high in this country and even more so abroad. Understanding its natural history and pathogenesis has improved but there are still many aspects of this complex infection that escape our understanding. For example, the immune system plays an important role both in causing liver damage and in its eradicating infection, but efforts thus far to heighten immune responses to improve viral clearance have failed. Nucleoside analogues are now available that are capable of lowering the viral burden, with resultant improvement in inflammation in the liver, but mutations arise frequently and the role of drugs in the management of patients with various phases of hepatitis B remains controversial. In addition, many patients with serious underlying liver disease are unaware of their disease or the clear benefits of treatment that accrue in most circumstances. New efforts at patient and physician education will be needed to reach the many patients who have infection and could benefit from care. Approximately 50% of patients with chronic hepatitis B in the US are of Asian ethnicity and many of these patients have disease that warrants treatment despite ALT values that fall within the standard reference range-treatment of this group is probably indicated but has not been tried in any controlled trial to date. The present RFA is intended to meet these challenges. Our proposal reviews current knowledge about hepatitis B, provides data on the burden of hepatitis B in the Dallas Fort Worth metroplex, and the strengths and experience of the investigators for future recruiting efforts for the proposed studies. We also provide the outline of a specific trial designs for a detailed database and to answer the concern raised, that is, to what extent do actively viremic Asian Americans with high normal aminotransferase levels benefit from a prolonged course of treatment with a potent, low resistance nucleoside analog.